Variant chr4-168877827-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The ENST00000507735.6(PALLD):c.-65C>A variant causes a 5 prime UTR change. The variant allele was found at a frequency of 0.00139 in 1,306,594 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 29 hom. )

Consequence

PALLD
ENST00000507735.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.80

Variant links:

Genes affected

PALLD (HGNC:17068): (palladin, cytoskeletal associated protein) This gene encodes a cytoskeletal protein that is required for organizing the actin cytoskeleton. The protein is a component of actin-containing microfilaments, and it is involved in the control of cell shape, adhesion, and contraction. Polymorphisms in this gene are associated with a susceptibility to pancreatic cancer type 1, and also with a risk for myocardial infarction. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

PALLD links:

CBR4 (HGNC:25891): (carbonyl reductase 4) Enables several functions, including 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity; NADPH binding activity; and NADPH dehydrogenase (quinone) activity. Involved in fatty acid biosynthetic process; glycoside metabolic process; and protein tetramerization. Located in mitochondrial matrix. Part of oxidoreductase complex. [provided by Alliance of Genome Resources, Apr 2022]

CBR4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP6

Variant 4-168877827-C-A is Benign according to our data. Variant chr4-168877827-C-A is described in ClinVar as [Benign]. Clinvar id is 1232402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00171 (260/151756) while in subpopulation EAS AF= 0.0357 (184/5152). AF 95% confidence interval is 0.0315. There are 2 homozygotes in gnomad4. There are 129 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 260 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PALLD	NM_001166108.2 linkuse as main transcript	c.1965-13095C>A		intron_variant		ENST00000505667.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PALLD	ENST00000505667.6 linkuse as main transcript	c.1965-13095C>A		intron_variant		1	NM_001166108.2	A2	Q8WX93-9

Frequencies

GnomAD3 genomes

AF:

0.00171

AC:

260

AN:

151648

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0356

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00212

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000339

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00153

AC:

AN:

26756

Hom.:

AF XY:

0.00131

AC XY:

AN XY:

16002

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00197

Gnomad EAS exome

AF:

0.0406

Gnomad SAS exome

AF:

0.00276

Gnomad FIN exome

AF:

0.000940

Gnomad NFE exome

AF:

0.000407

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.00134

AC:

1550

AN:

1154838

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

767

AN XY:

560700

show subpopulations

Gnomad4 AFR exome

AF:

0.0000854

Gnomad4 AMR exome

AF:

0.0000807

Gnomad4 ASJ exome

AF:

0.000502

Gnomad4 EAS exome

AF:

0.0437

Gnomad4 SAS exome

AF:

0.00355

Gnomad4 FIN exome

AF:

0.00240

Gnomad4 NFE exome

AF:

0.000143

Gnomad4 OTH exome

AF:

0.00203

GnomAD4 genome

AF:

0.00171

AC:

260

AN:

151756

Hom.:

Cov.:

AF XY:

0.00174

AC XY:

129

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.000197

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0357

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.00212

Gnomad4 NFE

AF:

0.000339

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000477

Hom.:

Bravo

AF:

0.00187

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over